title: The product of the Herpes simplex virus 1 UL7 gene interacts with a mitochondrial protein, adenine nucleotide translocator 2.
abstract: The herpes simplex virus 1 (HSV-1) UL7 gene is highly conserved among herpesviridae. Since the construction of recombinant HSV-1 with a mutation in the UL7 gene has not been reported, the involvement of HSV-1 UL7 in viral replication has been unclear. In this study, we succeeded in generating a UL7 null HSV-1 mutant virus, MT102, and characterized it. Our results were as follows. (i) In Vero cells, MT102 was replication-competent, but formed smaller plaques and yielded 10- to 100-fold fewer progeny than the wild-type virus, depending on the multiplicity of infection. (ii) Using mass spectrometry-based proteomics technology, we identified a cellular mitochondrial protein, adenine nucleotide translocator 2 (ANT2), as a UL7-interacting partner. (iii) When ANT2 was transiently expressed in COS-7 cells infected with HSV-1, ANT2 was specifically co-precipitated with UL7. (iv) Cell fractionation experiments with HSV-1-infected cells detected the UL7 protein in both the mitochondrial and cytosolic fractions, whereas ANT2 was detected only in the mitochondrial fraction. These results indicate the importance of HSV-1 UL7's involvement in viral replication and demonstrate that it interacts with ANT2 in infected cells. The potential biological significance of the interaction between UL7 and ANT2 is discussed.
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan. miti@nih.go.jp
authors.forename: Michiko
authors.initials: M
authors.lastname: Tanaka
authors.forename: Tetsutaro
authors.initials: T
authors.lastname: Sata
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawaguchi
mesh_terms: D033742:Adenine Nucleotide Translocator 2 / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002458:Cell Fractionation; D002522:Chlorocebus aethiops; D003600:Cytosol / Q000737:chemistry; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D047468:Immunoprecipitation; D008928:Mitochondria / Q000737:chemistry; D024101:Mitochondrial Proteins / Q000378:metabolism; D009154:Mutation; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011817:Rabbits; D014709:Vero Cells; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D033742:Adenine Nucleotide Translocator 2; D024101:Mitochondrial Proteins; C000597859:UL7 protein, human herpesvirus 1; D014763:Viral Matrix Proteins; D014764:Viral Proteins